Thanks to extensive sequencing efforts, myeloma can be grouped into subtypes based on the presence of certain genetic mutations. Patients participating in the trial will have their bone marrow biopsy sequenced, and based on that genetic data, will be assigned to the appropriate study arm.
Of the 6 treatment arms, 5 will include patients with “actionable” mutations. Patients in these arms will receive drugs that have been demonstrated to be effective against their particular mutations in other cancers. The sixth arm will treat patients whose cancers have no actionable mutations, and they will receive the standard-of-care regimen of ixazomib, pomalidomide, and dexamethasone.
The goals of the trial are 2-fold, says Dr Kumar. “One is obviously just proving the concept that treating patients differently based on some unique disease characteristic can change how those patients respond and their outcomes,” he says. Second would be demonstrating that a particular drug regimen works better than standard treatment, hopefully leading to a larger trial and incorporation of the therapy into standard clinical practice.
The results of the trial could have far-reaching consequences for how patients are treated. “We are moving from a way of treating patients that was based on the tissue of origin of cancers,” says Alessandro Laganà, PhD, assistant professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai, New York, New York. Dr Laganà published a study last year showing that RNA sequencing, in addition to DNA sequencing, could show the way to effective therapies for patients with refractory myeloma. 2
Because myeloma usually returns after treatment, and can become more aggressive with each relapse, patients with myeloma can quickly run out of options. The 64 patients participating in Dr Laganà’s study had received a median of 7 prior lines of therapy each before beginning the study. “We’re talking patients who have received all the possible options that have been approved for myeloma, and there’s nothing else,” he said. But in many cases, insurance denied the therapy that was indicated by the genetic data, because the drugs had been approved for cancers at other tissue sites of origin, not for blood cancers such as myeloma.
“This is certainly one thing that needs to change,” asserted Dr Laganà. He said he feels optimistic, though, that trials like his will eventually shift the paradigm of treatment from giving drugs based on the cancer type to giving them based on molecular data. “The more we prove that these approaches are beneficial to the patient, the more they will facilitate the changes in the way things are done,” he said.
And genetic sequencing is only 1 aspect of the molecular data that can direct treatment. “It’s not just genetics, there’s epigenetic markers, there’s protein markers — all of this has to be brought into a compendium of information,” said Dr Van Ness. “At what point is it irresponsible not to incorporate these kind of profiling methods?”
1. Harding T, Baughn L, Kumar S, Van Ness B. The future of myeloma precision medicine: integrating the compendium of known drug resistance mechanisms with emerging tumor profiling technologies. Leukemia. Published online January 25, 2019. doi: 10.1038/s41375-018-0362-z
2. Laganà A, Beno I, Melnekoff D, et al. Precision medicine for relapsed multiple myeloma on the basis of an integrative multiomics approach [published online August 8, 2018]. JCO Precis Oncol. doi: 10.1200/PO.18.00019